Dr Maria Kuznetsova

Environmental enrichment and physical exercise have many well-established health benefits. Although these environmental manipulations are known to delay symptom onset and progression in a variety of neurological and psychiatric conditions, the mechanisms underlying these effects remain poorly understood. A notable candidate molecular mechanism is that of microRNA, a family of small noncoding RNAs that are important regulators of gene expression. Research investigating the many diverse roles of microRNAs has greatly expanded over the past decade, with several promising preclinical and clinical studies highlighting the role of dysregulated microRNA expression (in the brain, blood and other peripheral systems) in understanding the aetiology of disease. Altered microRNA levels have also been described following environmental interventions such as exercise and environmental enrichment in non-clinical populations and wild-type animals, as well as in some brain disorders and associated preclinical models. Recent studies exploring the effects of stimulating environments on microRNA levels in the brain have revealed an array of changes that are likely to have important downstream effects on gene expression, and thus may regulate a variety of cellular processes. Here we review literature that explores the differential expression of microRNAs in rodents following environmental enrichment and exercise, in both healthy control animals and preclinical models of relevance to neurological and psychiatric disorders.

It is widely accepted that memory consolidation requires de-novo transcription of memory-related genes. Epigenetic modifications, particularly histone acetylation, may facilitate gene transcription, but their potential molecular targets are poorly characterized. In the current study, we addressed the question of epigenetic control of atypical protein kinases (aPKC) that are critically involved in memory consolidation and maintenance. We examined the patterns of expression of two aPKC genes (Prkci and Prkcz) in rat cultured cortical neurons treated with histone deacetylase inhibitors. Histone hyperacetylation in the promoter region of Prkci gene elicited direct activation of transcriptional machinery, resulting in increased production of PKC¿ mRNA. In parallel, histone hyperacetylation in the upstream promoter of Prkcz gene led to¿appearance of the corresponding PKC¿ transcripts that are almost absent in the brain in resting conditions. In contrast, histone hyperacetylation in the downstream promoter of Prkcz gene was accompanied by a decreased expression of the brain-specific PKM¿ products. We showed that epigenetically-triggered differential expression of PKM¿ and PKC¿ mRNA depended on protein synthesis. Summarizing, our results suggest that genes, encoding memory-related aPKC, may represent the molecular targets for epigenetic regulation through posttranslational histone modifications.

Background: Most data concerning chromosome organization have been acquired from studies of a small number of model organisms, the majority of which are mammals. In plants with large genomes, the chromosomes are significantly larger than the animal chromosomes that have been studied to date, and it is possible that chromosome condensation in such plants was modified during evolution. Here, we analyzed chromosome condensation and decondensation processes in order to find structural mechanisms that allowed for an increase in chromosome size. Results: We found that anaphase and telophase chromosomes of plants with large chromosomes (average 2C DNA content exceeded 0.8 pg per chromosome) contained chromatin-free cavities in their axial regions in contrast to well-characterized animal chromosomes, which have high chromatin density in the axial regions. Similar to animal chromosomes, two intermediates of chromatin folding were visible inside condensing (during prophase) and decondensing (during telophase) chromosomes of Nigella damascena: approximately 150 nm chromonemata and approximately 300 nm fibers. The spatial folding of the latter fibers occurs in a fundamentally different way than in animal chromosomes, which leads to the formation of chromosomes with axial chromatin-free cavities. Conclusion: Different compaction topology, but not the number of compaction levels, allowed for the evolution of increased chromosome size in plants.